Radiation Induced Lymphopenia Can Be Predicted by the Effective Dose to the Circulating Immune Cells (EDIC) in Breast Cancer.

PURPOSE/OBJECTIVE(S) Radiation induced lymphopenia (RIL) is a known risk factor for poor treatment outcome in breast cancers. In this study, we hypothesized that the effective dose to circulating immune cells (EDIC) predicted the severity of RIL in breast cancer. MATERIALS/METHODS Patients treated with adjuvant radiotherapy (RT) and with complete blood tests within one week from RT end/start (post/preRT) were eligible in this study. Radiation dosimetric factors were collected retrospectively. A previously reported EDIC model was used to estimate the equivalent uniform dose to the circulating blood according to the doses to blood-containing organs including lung, heart and total body. The primary study endpoint was RIL, which was the postRT lymphopenia defined by the CTCAE5.0 based on absolute peripheral lymphocyte count (PLC). Linear regression and normal tissue complication probability (NTCP) were used to develop models that predict postRT PLC from EDIC. RESULTS A total of 735 patients were eligible. The mean post/preRT PLC ratio was 0.66 (95% CI: 0.64-0.68) and mean EDIC of breast cancer was 1.7 Gy (95% CI: 1.6, 1.8). For patients with normal preRT PLC, postRT PLC was predicted as PLCpreRT *(0.90-0.16 * EDIC); for patients with preRT lymphopenia, postRT PLC was 1.05-0.17*EDIC. The RIL was also well described by the NTCP model with EDIC. The corresponding EDIC to induce 50% of grade-1, grade-2 and grade-3 RIL was 1.2, 2.1 and 3.7 Gy, respectively. CONCLUSION RIL may be predicted by EDIC in breast cancer, using either linear models or the conventional NTCP model. With further external validation, future radiation planning may consider EDIC for plan optimization.